Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)

Inclusion Criteria

• Locally recurrent and unresectable and/or distant metastatic differentiated thyroid cancer (DTC), histologically or cytologically confirmed; the diagnosis of DTC includes the following subtypes: papillary thyroid cancer (PTC) (including but not limited to variants such as follicular variant, tall cell, columnar cell, Hurthle cell variant of papillary carcinoma, and poorly differentiated), follicular thyroid cancer (FTC), including insular variant, Hurthle cell carcinoma and poorly differentiated thyroid cancer
• Measurable disease meeting the following criteria:
• At least 1 lesion of >= 1.0 cm in the longest diameter for a non-lymph node or >= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI); if there is only one target lesion and it is a non-lymph node, it should have a longest diameter of >= 1.5 cm
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
• For cohort 1 only: evidence of disease progression = = 600 mCi
• One or more measurable lesions that are fludeoxyglucose F-18 (FDG)-avid (> 5 standardized uptake value [SUV]), if positron emission tomography (PET)/CT scan performed; these lesions may also be RAI-avid
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count (ANC) >= 1, 500 /mcL (obtained = = 100,000 / mcL (obtained = = 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin dependency (= = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (obtained = 1.5 ULN (obtained = = 2.5 mg/dL (obtained = 1 year
• Male subjects: unwilling or unable to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive (HIV 1/2 antibodies) and currently receiving antiretroviral therapy
• Currently participating and receiving study therapy (except lenvatinib for patients in cohort 2) or has participated in a study of an investigational agent and received study therapy within 4 weeks prior to registration
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy = = 4 weeks prior to registration
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 (except lenvatinib for patients in cohort 2) or who has not recovered (i.e., = = 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); NOTE: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Known history of, or any evidence of active, non-infectious pneumonitis that required steroids
• Active infection requiring systemic therapy
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known psychiatric or